The objective of this project is to encapsulate purified antigens of B. pertussis into biodegradable, biocompatible microspheres in an immunogenic form for use as an experimental oral pertussis vaccine in an animal model of B. pertussis infection. We have shown that B. pertussis filamentous hemagglutinin (FHA), pertussis toxin, pertactin (69 K outer membrane protein), and whole formalin fixed B. pertussis remain immunogenic after encapsulation in biocompatible, biodegradable microspheres. Oral administration of high doses of microencapsulated antigens neither protected mice from B. pertussis infection, nor elicited mucosal antibody. In contrast, intranasal administration of small doses of microencapsulated antigens induced both IgG and IgA antibodies to B. pertussis antigens in respiratory secretions, as well as protected mice against infection. However, the same low doses of unencapsulated antigens administered intranasally neither protected nor stimulated specific mucosal antibody. This work has established that microencapsulation of pertussis antigens has an adjuvant effect for intranasal delivery. Experiments to study the immunologic mechanisms involved in immune stimulation by microcapsules are currently in progress. The significance of this project lies in its application to the development of mucosal vaccine for pertussis.